Research Component # 3, entitled Post-Abstinence Response Drinking in Humans will assess the effect of 2 weeks of monitored abstinence from usual drinking habits on post-abstinence response (PAR) dnnking using an operant alcohol self-administration paradigm. The sample population is 60 healthy Caucasian, young- adult, heavy drinkers. The central hypotheses are that short term abstinence from alcohol will increase PAR in binge-style dnnkers, compared to those who consume a similar quaiitity over time, but on a regular basis, and that PAR will be greater in those with positive family of alcoholism compared to controls. We will also explore a panel of candidate genes, the personal history of externalizing behaviors, and changes in metabolic capacity for eliminating alcohol for potential associations with PAR. PAR will be assessed in a 3-session, within-subjects, between-group design using the Progressive Work Paradigm of the Computer-Assisted Self-Administration of Ethanol (CASE) system developed by the lARC and validated in Pilot Study 53 of the current research cycle. The first session will provide familiarity with the procedures, and the second and third sessions will be conducted on the days that bracket 2 weeks of monitored abstinence from the subject's usual drinking habits. Indices of the subject's maximal willingness to perform increasing amounts of work to earn immediate delivery of another alcohol reward, and the subjective perceptions of craving and alcohol effects will provide the dependent measures for analysis. The combination of intravenous alcohol delivery and physiologically-based pharmacokinetic modeling of individual subjects that is employed by CASE insures that, unlike oral alcohol administration, the incremental time course of brain exposure to alcohol will be the same for each reward in every subject, and will be free of expectancies associated with sight, taste and odor. We expect the research to establish a new endophenotype for alcoholism risk, PAR; enabling future research on the influence of specific genes and/or epigenetic mediators, PAR's neural substrates, the efficacy of pharmaceuticals on blunting development of binge dnnking, and the interaction of abstinence from alcohol with use of other drugs.